Prognostic implications of left ventricular myocardial work indices in cardiac amyloidosis.

AIMS: Left ventricular (LV) myocardial work index (LVMWI) derived from pressure-strain analysis resembles a novel non-invasive method for LV function evaluation. LV global longitudinal strain (LVGLS) has proven beneficial for risk stratification in cardiac amyloidosis (CA) patients. This study aimed to evaluate the potential additive value of LVMWI for outcome prediction in CA patients. METHODS AND RESULTS: We enrolled 100 CA patients in the period 2014-19 from Aarhus University Hospital, Denmark and Uppsala University Hospital, Sweden. All patients underwent comprehensive echocardiographic evaluation and were prospectively followed until censuring date on 31 March 2019 or death. During follow-up, we registered major adverse cardiac events (MACE) comprising heart failure requiring hospitalization and all-cause mortality. The median follow-up was 490 (228-895) days. During follow-up, a total of 42% of patients experienced MACE and 29% died. Patients with LVMWI <1043 mmHg% had higher MACE risk than patients with LVMWI >1043 mmHg% [hazard ratio (HR) 2.3, 95% confidence interval (CI) 1.2-4.3; P = 0.01]. Furthermore, patients with LVMWI <1039 mmHg% also had higher all-cause mortality risk than patients with LVMWI >1039 mmHg% (HR 2.6, 95% CI 1.2-5.5; P < 0.05). Moreover, the apical-to-basal segmental work ratio was a significant MACE and all-cause mortality predictor. By combining LVMWI and apical-to-basal segmental work ratio, we obtained an independent model for all-cause mortality prediction (high vs. low risk: HR 6.4, 95% CI 2.4-17.1; P < 0.0001). In contrast, LVGLS did not predict all-cause mortality. CONCLUSION: LV myocardial work may be of prognostic value in CA patients by predicting both MACE and all-cause mortality.

Diagnostic Accuracy of [11C]PIB Positron Emission Tomography for Detection of Cardiac Amyloidosis.

OBJECTIVES: This dual-site study evaluated the diagnostic accuracy of the method. BACKGROUND: Pittsburgh compound ([11C]PIB) positron emission tomography (PIB-PET) has shown promise as a specific and noninvasive method for the diagnosis of cardiac amyloidosis (CA). METHODS: The study had 2 parts. In the initial study, 51 subjects were included, 36 patients with known CA and increased wall thickness (15 immunoglobulin light chain [AL] and 21 transthyretin [ATTR] amyloidosis) and 15 control patients (7 were nonamyloid hypertrophic and 8 healthy volunteers). Subjects underwent PIB-PET and echocardiography. Sensitivity and specificity of PIB-PET were established for 2 simple semiquantitative approaches, standardized uptake value ratio (SUVR) and retention index (RI). The second part of the study included 11 amyloidosis patients (5 AL and 6 hereditary ATTR) without increased wall thickness to which the optimal cutoff values of SUVR (>1.09) and RI (>0.037 min-1) were applied prospectively. RESULTS: The diagnostic accuracy of visual inspection of [11C]PIB uptake was 100% in discriminating CA patients with increased wall thickness from controls. Semiquantitative [11C]PIB uptake discriminated CA from controls with a 94% (95% confidence interval [CI]: 80% to 99%) sensitivity for both SUVR and RI and specificity of 93% (95% CI: 66% to 100%) for SUVR and 100% (95% CI: 75% to 100%) for RI. [11C]PIB uptake was significantly higher in AL-CA than in ATTR-CA patients (p < 0.001) and discriminated AL-CA from controls with 100% (95% CI: 88% to 100%) accuracy for both the semiquantitative measures. In the prospective group without increased wall thickness, RI was elevated compared to controls (p = 0.001) and 5 of 11 subjects were evaluated as [11C]PIB PET positive. CONCLUSIONS: In a dual-center setting, [11C]PIB PET was highly accurate in detecting cardiac involvement in the main amyloid subtypes, with 100% accuracy in AL amyloidosis. A proportion of amyloidosis patients without known cardiac involvement were [11C]PIB PET positive, indicating that the method may detect early stages of CA.

Left Ventricular Pressure-Strain-Derived Myocardial Work at Rest and during Exercise in Patients with Cardiac Amyloidosis.

BACKGROUND: Left ventricular pressure-strain-derived myocardial work index (LVMWI) is a novel, noninvasive method for left ventricular (LV) function evaluation in relation to LV pressure dynamics. LV global longitudinal strain (LVGLS) has proven benefit for diagnosis and risk stratification in patients with cardiac amyloidosis (CA), but LVGLS does not adjust for loading conditions. The aim of the present study was to characterize LVMWI at rest and during exercise in patients with CA. METHODS: A total of 155 subjects were retrospectively included. These subjects comprised 100 patients with CA and 55 healthy control subjects. All patients had previously undergone comprehensive two-dimensional echocardiographic examinations at rest. Furthermore, a subgroup 27 patients with CA and 41 control subjects was examined using semisupine exercise stress echocardiography. RESULTS: Patients with CA had significantly lower LVGLS, LVMWI, and LV myocardial work efficiency (LVMWE) than control subjects (P < .0001 for all). The reduction in LV myocardial performance was more pronounced in the basal segments, which led to significant alterations in the average apical-to-basal segmental ratios between patients with CA and control subjects (LVGLS, 2.6 [1.9 to 4.1] vs 1.3 [1.2 to 1.5]; LVMWI, 2.6 [1.7 to 3.8] vs 1.3 [1.1 to 1.5]; LVMWE, 1.1 [1.0 to 1.3] vs 1.0 [1.0 to 1.1]; P < .0001 for all). The average increase in LVMWI from rest to peak exercise was 1,974 mm Hg% (95% CI, 1,699 to 2,250 mm Hg%; P < .0001) in control subjects and 496 mm Hg% (95% CI, 156 to 835 mm Hg%; P < .01) in patients with CA. The absolute numeric LVGLS increase was 5.6% (95% CI, 3.9% to 7.3%; P < .0001) in control subjects and only 1.2% (95% CI, -0.9% to 3.3%; P = .26) in patients with CA (between groups, P < .0001) from rest to peak exercise. The LVMWI increase in patients with CA was mediated by improvement in the apical segments (P < .0001), whereas there was no significant LVMWI alterations in the midventricular or basal segments. LVMWE remained stable during exercise in control subjects (Δ -0.6%; 95% CI, -2.5% to 1.2%; P = .50) but decreased significantly in patients with CA (Δ -2.5%; 95% CI, -4.8% to -0.2%; P < .05). CONCLUSIONS: Patients with CA have significantly reduced magnitude of LVMWI compared with healthy control subjects. With exercise, the differences are even more pronounced. Even though LVMWI increased with exercise, LVMWE decreased, suggesting inefficient myocardial energy exploitation in patients with CA.

Myocardial Oxygen Consumption and Efficiency in Patients With Cardiac Amyloidosis.

Background This study evaluated myocardial oxygen consumption (MVO2) and myocardial external efficiency (MEE) in patients with cardiac amyloidosis (CA). Furthermore, we compared MEE and MVO2 in subjects with light chain amyloidosis versus transthyretin (ATTR) amyloidosis. Methods and Results The study population comprised 40 subjects: 25 patients with confirmed CA and 15 control subjects. All subjects underwent an 11C-acetate positron emission tomography. Furthermore, the CA patients underwent comprehensive echocardiography and right heart catheterization during a symptom-limited, semi-supine exercise test. MEE was calculated from 11C-acetate positron emission tomography as the ratio of left ventricular (LV) stroke work and the energy equivalent of MVO2. Myocardial work efficiency was calculated as echocardiography-derived work pressure product divided by three-dimensional LV mass. CA patients had significantly lower LV-ejection fraction (54±13% versus 63±4%, P<0.05) and LV-global longitudinal strain (LVGLS) (12±4% versus 19±2%, P<0.0001) and a more restrictive filling pattern (E/e'-ratio 18 [12-25] versus 8 [7-9], P<0.0001) than controls. MEE was severely reduced (13±5% versus 22±5%, P<0.0001) whereas total MVO2 was higher (18±6 mL/min versus 13±3 mL/min, P<0.01) in CA patients than controls. MEE decreased with increasing New York Heart Association symptom burden ( P<0.0001). We found a good relationship between MEE and peak exercise systolic performance (LVGLS: R2=0.60, P<0.0001; myocardial work efficiency: R2=0.48, P<0.0001; cardiac index: R2=0.52, P<0.0001) and between MEE and myocardial blood flow ( R2=0.44, P<0.0001). Conclusion Myocardial oxidative metabolism is disturbed in CA patients with increased total MVO2 and reduced MEE. MEE correlated significantly with echocardiographic derived systolic parameters such as myocardial work efficiency and LVGLS that might be used as surrogate MEE markers.